A Pyridine–Pyridine Cross‐Coupling Reaction via Dearomatized Radical Intermediates

• Published in: Angewandte Chemie International Edition Vol. 58; no. 42; pp. 14882 - 14886
• Main Authors: Koniarczyk, J. Luke, Greenwood, Jacob W., Alegre‐Requena, Juan V., Paton, Robert S., McNally, Andrew
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.10.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: bipyridines; Chemical industry; Chemistry; Chemistry, Multidisciplinary; Coupling; Intermediates; Minisci reaction; phosphonium salts; Physical Sciences; Pyridines; radical anions; radical coupling; Reagents; Salts; Science & Technology; Selectivity; bipyridines; ELECTRON; radical anions; phosphonium salts; ARYLATION; TRIPHENYL; radical coupling; C-H FUNCTIONALIZATION; HETEROCYCLES; SUBSTITUTIONS; RATE CONSTANTS; Minisci reaction; CHEMISTRY; ARYL RADICALS; TRIFLUOROMETHYLATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201906267

A pyridine–pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2pin2 as an electron‐transfer reagent. Complete regio‐ and cross‐selectivity are observed when forming a range of valuable 2,4′‐bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci‐type coupling involving a pyridyl radical. Instead, a radical–radical coupling process between a boryl phosphonium pyridyl radical and a boryl‐stabilized cyanopyridine radical explains the C−C bond‐forming step. Pyridyl phosphonium salts react with cyanopyridines and B2pin2 to form 2,4‐bipyridines with complete regiocontrol. Mechanistic studies support a radical–radical coupling process between two boryl‐stabilized pyridyl radical anions rather than a Minisci‐type pathway, and the process is unique to pyridyl phosphonium salts.